Mass spectrometry is an analytical methodology used for quantitative molecular analysis of analytes in a sample. Analytes in a sample are ionized, separated according to their mass by a spectrometer and detected to produce a mass spectrum. The mass spectrum provides information about the masses and in some cases the quantities of the various analytes that make up the sample. In particular embodiments, mass spectrometry can be used to determine the molecular weight or the molecular structure of an analyte in a sample. Because mass spectrometry is fast, specific and sensitive, mass spectrometer devices have been widely used for the rapid identification and characterization of biological analytes.
Mass spectrometers may be configured in many different ways, but are generally distinguishable by the ionization methods employed and the ion separation methods employed. For example, in certain devices parent analyte ions are isolated, the parent ions are fragmented to produce daughter ions and the daughter ions are subjected to mass analysis. The identity and/or structure of the parent analyte ion can be deduced from the masses of the daughter ions. Such devices, generally referred to as tandem mass spectrometers (or MS/MS devices) may be coupled with a liquid chromatography system (e.g., an HPLC system or the like) and a suitable ion source (e.g. an electrospray ion source) to investigate analytes in a liquid sample.
In a mass spectrometer, analyte molecules are ionized in an ion source. The masses of the resultant ions are determined in a vacuum by a mass analyzer that measures the mass/charge (m/z) ratio of the ions. When used in conjunction with a liquid chromatography device, a mass spectrometer can provide information on the molecular weight and chemical structure of compounds separated by the chromatography device, allowing identification of those components.
Mass spectrometer systems generally contain a primary ion path down which ions are transported from a primary ion source (e.g., a source of analyte ions) to a mass spectrometer. In many instances it is desirable to controllably introduce ions produced by a second ion source into the primary ion path. For example, in certain embodiments it is sometimes desirable to introduce ions of known mass and charge, so called “calibration standards”, “reference mass standards” or “internal standards”, into an ion stream containing analyte ions of interest in order to provide a more accurate measurement of the molecular mass of those analytes. In addition, it is sometimes desirable to be able to analyze ions produced by two distinct ion sources in the same mass spectrometer, either simultaneously or in series, without having to disconnect and reconnect any apparatus. Further, it is sometimes desirable to introduce additional ions into a primary ion path in order that the additional ions collide with the primary ions to physically or chemically change (e.g., change the charge of, reduce the energy of, or fragment) the ions in the primary ion path.
Various systems for introducing a second ion beam into a primary ion path in a mass spectrometer are known. For example, a “Y”-shaped sampling device may be used to combine different ions as they exit an ion source (see, e.g., Smith et al J. Mass. Spec. Rev. 1991 10: 359-451), a quadrupole ion deflector may be used to direct ion streams into a common ion guide (see, e.g., U.S. Pat. No. 6,596,989), and ion beams may be introduced into opposite sides of a linear ion trap and are combined within the trap (see, e.g., Syka et al, Proc. Natl. Acad. Sci. 2004 101:9528-9533). However, these systems generally lack flexibility, are impractical for many purposes, or greatly decrease the sensitivity of the ion detection for the primary ions.
Accordingly, a need exists for new means for introducing a secondary ion stream into a primary ion path. This invention meets this need, and others.